Associations between daily aspirin use and cancer risk across strata of major cancer risk factors in two large U.S. cohorts

Purpose: Daily aspirin use has been shown to reduce risk of colorectal, and possibly other, cancers, but it is unknown if these benefits are consistent across subgroups of people with differing cancer risk factors. We investigated whether age, body mass index (BMI), smoking status, physical inactivity, and family history of cancer modify the effect of daily aspirin use on colorectal, ovarian, breast, endometrial and aggressive prostate cancer risk. Methods: We pooled 423,495 individuals from two prospective, U.S.-based studies: the NIH-AARP Diet and Health Study (1995–2011) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (1993–2009). Using Cox proportional hazards regression, we examined associations between daily aspirin use (≥ 5 days/week) and risk of colorectal, ovarian, breast, endometrial, and aggressive prostate cancer, overall and across strata of risk factors. Results: Daily aspirin use was associated with a 15% reduction in colorectal cancer risk (hazard ratio [HR]: 0.85, 95% confidence interval [CI] 0.80–0.89). Risk reductions were generally consistent across strata of risk factors but attenuated with increasing BMI (p-interaction = 0.16). For ovarian cancer, there was no significant association overall (HR: 0.93, 95% CI 0.80–1.08) but reduced risk among obese women (HR: 0.73, 95% CI 0.52–0.98, p-interaction = 0.12). Weak or null associations were observed for breast, endometrial, and aggressive prostate cancer, with no strong effect modification observed. Conclusions: Daily aspirin use appears to reduce colorectal cancer risk regardless of other risk factors, though the potential modifying effect of BMI warrants further investigation and may need to be considered in risk–benefit calculations for aspirin use.